Operator: And our next question will come from the line of Anupam Rama from J.P. Morgan.
Malcolm Kuno: This is actually Malcolm on for Anupam. So just one from us. What is being assumed in terms of milestones between now and your cash runway into 2026?
Victor Perlroth: Well, certainly, the completion of the two tarcosimab pivotals as well as the completion of the 501 pivotal. And we’re in discussions with FDA currently on the design of the Phase 2b/3 studies for 101. And depending a little bit on those designs and how they translate into enrollment, we’re hopeful that we’ll be able to get those studies out in that timeframe as well.
Operator: [Operator Instructions] Our next question comes from the line of Andrea Tan from Goldman Sachs.
Andrea Tan: Two for us please. Maybe as a follow up to a prior comment, recognizing that the potency remains the same between the two formulations that you have. Can you share what may — or maybe speak to what data you’ve seen that supports that durability of the original formulation will carry over as you transition from the biopolymer conjugate to now a mix of the conjugate plus free antibody?
Victor Perlroth: We believe more broadly that disease variability in patients is what drives durability more strongly than the amount of conjugate that we have. So for example, in our Phase 1b study, we tested 2.5 mgs versus 5 mgs of fully conjugated material. And there’s very little distinction between the durability that we saw on the 2.5 milligram dose and the 5 milligram dose. So as we bring the level of conjugate down on the margin to allow a broader amount of free protein, we believe that we can bring the best of both worlds into both the tarcosimab and the KSI-501 formulations without impacting durability and creating a powerful medicine for patients.
Andrea Tan: And then just maybe one quickly on the Phase 1 data that you have seen in DME for the 16 patients from the Phase 1. Could you just share or speak a little bit more about what gives you the confidence to move directly from that in the 16 patients to a Phase 3 trial now in wet AMD?
Victor Perlroth: I think the important point about the Phase 1 study with KSI-501 was to gauge safety as well as to gauge bioactivity in terms of vision and OCT. And given the broad overlap across the retinal vascular diseases and with the existing agents, the idea of starting in DME where you can see predictable responses of bioactivity and safety and then using that kind of as a point of departure into any number of the different diseases. So I mean, the four reasons that give us confidence to move directly into Phase 3 in wet AMD based on the KSI-501 Phase 1 is, one, I mean the durability profile of the platform. Two, the dual mechanism of action, right, with best in class of VEGF inhibition from the trap and where we also target IL 6, which is a known culprit of suboptimal response and reactivation of disease in wet AMD.
Third is our enhanced formulation. And four, the 10 years of design, the manufacturing and the clinical and the operational experience that we have, the three INDs, the three molecules in clinical phase, the two first in human studies, the eight clinical trials, seven of them pivotal. So we’re not starting from scratch here. And furthermore, in the future, we may be thinking of exploring KSI-501 and DME and RVO as well.
Operator: Our next question will come from line of Gena Wang from Barclays.
Gena Wang: Victor, based on current data, do you believe 501 is better than tarcocimab? And a related question is for DAYBREAK. Other than being cost effective to avoid running an independent Phase 3 study for tarcocimab, will you try to design in a way to power to show the clinical benefit differences between 501 versus tarcocimab?
Victor Perlroth: I don’t think it’s important whether tarcocimab or 501, whether one is better than the other. There’s clearly an opportunity for, let’s say, a twice a year in the majority of patients anti-VEGF agent, and tarcocimab is just needs to get pushed over the finish line and why don’t we see how physicians like it. And by running GLOW2 and having that tuck in group and the DAYBREAK study and wet AMD, we’re going to be creating a useful amount of data for physicians, for tarcocimab. It’s not our objective to power a distinction between tarcocimab and 501 in DAYBREAK. I mean if 501 showed maybe some trend that it was better than aflibercept or better than tarcocimab, we see that as very positive because we’re obsoleting those agents with our own agent.
And the question there for the 501 program is it’s going to need a second pivotal. And so, at what point do we think it would be useful and important to start that, such that it’s a molecule that could be on a point — a path to enter the market? I mean, if both molecules perform as we hope, right, tarcocimab and 501 showing a differentiated durability profile and they both meet the primary endpoint, it’s a problem that we would be delighted to have.
Operator: Our next question will comes from the line of Ellie Merle from UBS.
Samantha Meadows: It’s Sam on for Ellie. We just had two questions. I guess first, where do you think about how IL-6 inflammation is, or like where do you think IL-6 inflammation is particularly relevant in the context of this space? And then I’ll ask my second after.
